Analysis of the cervical microbiome and potential biomarkers from postpartum HIV-positive women displaying cervical intraepithelial lesions

Abstract

The cervical microbiota composition and diversity of HIV-positive women in the postpartum period is unknown. Using a high-throughput bacterial 16S rRNA gene sequencing, we identified four community state types (CSTs). CST III (Lactobacillusdominant) and CST IV (IV-A, IV-B.1, IV-B.2; high-diversity) were found in 41% and 59% of samples, respectively. We did not find association of any CST to postpartum period (six or twelve months), HPV infection or cytology (normal or lesion). However, five bacterial genera were associated with cervical lesions (Gardnerella, Aerococcus, Schlegelella, Moryella and Bifidobacterium), with significant odds ratio (OR) of 40 (2.28–706) for the presence of Moryella and 3.5 (1.36–8.9) for Schlegelella. Longitudinal analysis of samples at postpartum that regressed (lesion to normal), progressed (normal to lesion) and maintained the cytology (lesion or normal) evidenced Gardnerella with a significantly higher abundance in regressing lesions. In the current study, we report the first data on the cervical microbiota of HIV-positive women in the postpartum period. Consistent with previous studies of HIV-negative cohorts, HIV-positive women present a stable cervical microbiota of high-diversity in the postpartum period. Our results highlight that specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with cervical lesions.

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

“…HIV-positive women show increased risk of HPV acquisition and CIN development [106][107][108]. A study that analyzed the cervicovaginal microbiome in the postpartum period of HIV-positive women showed a high frequency of L. iners, Moryella, Schlegelella, and Gardnerella associated with CIN with significant odds ratios of 40 for Moryella and of 3.5 for Schlegelella [12]. In a longitudinal analysis, when comparing the bacterial microbiome of women that showed CIN regression to normal cytology, Gardnerella appeared with a higher frequency in CIN when compared to normal status [12].…”

“…A study that analyzed the cervicovaginal microbiome in the postpartum period of HIV-positive women showed a high frequency of L. iners, Moryella, Schlegelella, and Gardnerella associated with CIN with significant odds ratios of 40 for Moryella and of 3.5 for Schlegelella [12]. In a longitudinal analysis, when comparing the bacterial microbiome of women that showed CIN regression to normal cytology, Gardnerella appeared with a higher frequency in CIN when compared to normal status [12]. Similarly, a report from HIV+ pregnant women in Zambia showed that they had higher microbiome diversity, greater abundance of G. vaginalis and A. vaginae and lack of L. crispatus when compared to HIV-pregnant participants.…”

“…The bacterial abundance in the cervicovaginal microenvironment is variable and the term CST is used to indicate the dominant species present, as described above. CST IV is the most diverse type and has bacterial species linked with CIN, such as Gardnerella, Prevotella, and Atopobium as dominant species, and other diverse species with variable abundance, like Anaerococcus sp., Peptostreptococcus sp., Fusobacterium sp., Moryella, Sneathia, and Schlegelella [11][12][13]. The current approach to detect bacterial species in scientific studies is the 16S-HTS.…”

“…The cervical microenvironment is complex, composed of immune cells and its specific microbiota that modulate local immune responses [7][8][9]. Recently, some studies have shown an association between the cervicovaginal microbiome and HPV infection, as well as CIN and CC [9][10][11][12][13][14]. In the current review, we describe the cervicovaginal microbiome landscape and its influence on the modulation of cervical viral infections, in addition to its role as a biomarker with predictive value for HPV infection and cervical neoplasia progression.…”

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

“…Further viral and cellular proteins might be excellent candidate indicators of disease, e.g., HPV L1 protein, Claudin-1, VCP, and E-cadherin, which have promising results in research [190][191][192][193][194]. Alternatively, the vaginal microbiome might be used to distinguish progression vs. regression of disease [195][196][197]. The overall results from existing and candidate biomarkers evidence their utility in profiling the risk for disease.…”